Abstract 94P
Background
The Italian Register of Actionable Mutations (RATIONAL) was created to collect Next-Generation-Sequencing (NGS)-based tumor profiling data. RATIONAL wants to facilitate the identification of subgroups of patients who might benefit of targeted therapies. In this respect, we classified the molecular alterations collected in the register according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT).
Methods
The RATIONAL study is an Italian multicenter, observational and prospective clinical trial. The primary aim of the study is the description of the frequency of actionable mutations in the cohort of enrolled patients. The study enrolled patients who already had available a NGS-based profiling of the tumor (Pathway A) or underwent a comprehensive tumor profiling with the FoundationOne CDx assay within the trial (Pathway B).
Results
Sequencing data are available for 611 patients. The most common tumor types are lung cancer (46% of cases), tumors of the biliary tract (18%), colorectal (8%), gastric (4%) and breast (3%) cancers. Cancers of unknown primary (CUP) account for 9% of cases. In 92% of patients, at least one genomic alteration was detected. Collectively, 2594 genomic alterations in 254 genes were identified. The most frequently altered gene was TP53 (53% of cases), followed by KRAS (27%), EGFR (12%), CDKN2A/B (11%) and PIK3CA (10%). We categorized molecular alterations according to the ESCAT scale, for 444 cases belonging to lung carcinoma, cholangiocarcinoma, colorectal, gastric and breast cancer. We found that 21.6% (96/444) of patients had genomic alterations classified in the level I, with values ranging from 8.9% for colorectal cancer to 52% of gastric cancer. Furthermore, 12.16% of patients had molecular alterations classified in level II and 11.48% in level III. Among patients with CUP, 25/53 (47%) had genomic alterations for which approved drugs for different indications are available.
Conclusions
The creation of a national registry of tumor genomic data facilitates the clustering of patients based on their molecular profile. The ESCAT scale might help categorize clinically relevant molecular alterations for improving therapeutic strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
FICOG.
Funding
AstraZeneca, Roche, BMS and Daiichi Sankyo.
Disclosure
All authors have declared no conflicts of interest.